Summary: Currently, enhanced inactivated poliovirus vaccine (eIPV) are produced using wild-type poliovirus strains as substrates. The strains possess high pathogenic potential and if they were to be accidentally released from manufacturing areas into communities (and such an accident has actually occurred) they might be responsible for outbreaks of poliomyelitis. After eradication of poliomyelitis is completed, work with wild-type polioviruses will require strict containment measures, which will demand serious changes in the manufacturing process to protect surrounding communities, and to prevent potentially catastrophic consequences of poliovirus release. An attractive alternative approach to safety of eIPV production would be to switch to using non-pathogenic strains of poliovirus. Direct evaluation of efficacy of these new IPV as well as of combination vaccines containing IPV component is not possible, and therefore any regulatory actions should rely on surrogate immunogenicity data. In our previous studies we have shown that wild-type MEF-1 strain used fro production of IPV differs significantly from Sabin 2 strain used for OPV production, suggesting that these vaccines may have different immunogenicity. The Tg-mouse immunizaiton - challenge test showed that conventional IPV provides good protection against challenge with both wild-type strain and with vaccine-derived virus, while IPV prepared from Sabin 2 strain only protects against challenge with homologous virus. In vitro ELISA test also confirmed that MEF-1 has a broader immunogenicity than Sabin 2 strain, suggesting that should IPV be produced from Sabin 2 strain, its immunizaiton regiomen may need to be adjusted for maximum efficacy. We have also developed an improved ELISA test for potency testing of IPV, as well as for consistency monitoring of IPV production. Respective reference reagents were developed. The first method is based on direct ELISA with polyclonal IgG and biotin-avidin conjugates. The consistency test takes advantage of block-ELISA test with monoclonal antibodies, and allows us to determine epitope profiles of inactivated vaccines as well as of strains isolated from vaccine-associated cases caused by OPV. The future directions of this project will include studies of IgA antibodies in saliva as a rapid method for evaluation of immunogenicity of poliovirus vaccines, and further development of epitope profiling.